13,14-Didehydro-inter-oxa-11-deoxy-11-hydroxymethyl-19-oxo-PGE1 compounds

ABSTRACT

The present invention provides novel 13,14-didehydro-5-oxa-11-deoxy-11-hydroxymethyl-19-oxo-PGE 1  compounds, which are useful for a variety of pharmacological purposes, e.g., antiasthmatic indications.

CROSS REFERENCE TO RELATED APPLICATION

This application is a division of Ser. No. 025,879, filed Apr. 2, 1979,now pending.

DESCRIPTION

1. Background of the Invention

The present invention relates to novel prostaglandin analogs.Particularly, the invention relates to prostaglandin analogs wherein theC-19 position is substituted by oxo, i.e., 19-keto-PG compounds or19-oxo-PG compounds. Most particularly, the present invention relates tonovel 13,14-Didehydro-inter-oxa-11-deoxy-11-hydroxymethyl-19-oxo-PGE₁compounds, a disclosure of the preparation and pharmacological use ofwhich is incorporated here by reference from U.S. Pat. No. 4,228,104.

2. Prior Art

Prostaglandins exhibiting a variety of substitution at the C-19 positionare known. See particularly J. C. Sih, et al., JACS 91:3685 (1969)wherein 19-oxo-PGE₂ and 13,14-dihydro-19-oxo-PGE₁ are disclosed.Further, Chemical Abstracts 86:43265H purportedly discloses 19-oxo-PGF₂α. The abstract is derived from Japanese Kokai No. 76 82,245.

SUMMARY OF THE INVENTION

The present invention particularly provides:

a compound of the formula ##STR1## wherein D is (1) (CH₂)₃ --O--CH₂ --,

(2) (CH₂)₂ --O--(CH₂)₂ --, or

(3) --CH₂ --O--(CH₂)₃ --;

wherein g is zero, one, two, or three;

wherein Q is α--OH:β--R₅ or α--R₅ :β--OH, wherein R₅ is hydrogen ormethyl;

wherein R₆ is

(a) hydrogen,

(b) alkyl of one to 12 carbon atoms, inclusive,

(c) cycloalkyl of 3 to 10 carbon atoms, inclusive,

(d) aralkyl of 7 to 12 carbon atoms, inclusive,

(e) phenyl,

(f) phenyl substituted with one, 2, or 3 chloro or alkyl groups of oneto 3 carbon atoms, inclusive,

(g) --(p-Ph)--CO--CH₃,

(h) --(p-Ph)--NH--CO--(p-Ph)--NH--CO--CH₃,

(i) --(p-Ph)--NH--CO--(p-Ph),

(j) --(p-Ph)--NH--CO--CH₃,

(k) --(p-Ph)--NH--CO--NH₂,

(l) --(p-Ph)--CH═N--NH--CO--NH₂,

(m) β-naphthyl,

(n) --CH₂ --CO--R₂₈,

wherein (p-Ph) is para-phenyl or inter-para-phenylene,

wherein R₂₈ is phenyl, p-bromophenyl, p-biphenyl, p-nitrophenyl,p-benzamidophenyl, or 2-naphthyl, or

(o) a pharmacologically acceptable cation;

wherein R₃ and R₄ are hydrogen, methyl, or fluoro, being the same ordifferent, with the proviso that one of R₃ and R₄ is fluoro only whenthe other is hydrogen or fluoro; and

wherein X is --C═C--.

The compounds of the present invention are particularly useful forinducing prostaglandin-like biological effects, as described in UnitedStates Ser. No. 026,066. Uses of compounds in accordance with thepresent invention include, therefore, antiasthmatic indications.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention particularly relates to:

13,14-didehydro-5-oxa-11-deoxy-11-hydroxymethyl-19-oxo-PGE₁, and

13,14-didehydro-5-oxa-11-deoxy-11-hydroxymethyl-15(R)-19-oxo-PGE₁.

I claim:
 1. A compound of the formula ##STR2## wherein D is (1) (CH₂)₃--O--CH₂ --,(2) (CH₂)₂ --O--(CH₂)₂ --, or (3) --CH₂ --O--(CH₂)₃ --;wherein Q is α--OH:β--R₅ or α--R₅ :β--OH, wherein R₅ is hydrogen ormethyl; wherein R₆ is(a) hydrogen, (b) alkyl of one to 12 carbon atoms,inclusive, (c) cycloalkyl of 3 to 10 carbon atoms, inclusive, (d)aralkyl of 7 to 12 carbon atoms, inclusive, (e) phenyl, (f) phenylsubstituted with one, 2, or 3 chloro or alkyl groups of one to 3 carbonatoms, inclusive, (g) --(p-Ph)--CO--CH₃, (h)--(p-Ph)--NH--CO--(p-Ph)--NH--CO--CH₃, (i) --(p-Ph)--NH--CO--(p-Ph), (j)--(p-Ph)--NH--CO--CH₃, (k) --(p-Ph)--NH--CO--NH₂, (l)--(p-Ph)--CH═N--NH--CO--NH₂, (m) β-naphthyl, (n) --CH₂ --CO--R₂₈,wherein (p-Ph) is para-phenyl or inter-para-phenylene, wherein R₂₈ isphenyl, p-bromophenyl, p-biphenyl, p-nitrophenyl, p-benzamidophenyl, or2-naphthyl, or(o) a pharmacologically acceptable cation; wherein R₃ andR₄ are hydrogen, methyl, or fluoro, being the same or different, withthe proviso that one of R₃ and R₄ is fluoro only when the other ishydrogen or fluoro; and wherein X is --C═C--.
 2. A compound according toclaim 1, wherein R₆ is hydrogen or methyl. 3.13,14-Didehydro-5-oxa-11-deoxy-11-hydroxymethyl-19-oxo-PGE₁, a compoundaccording to claim
 2. 4.13,14-Didehydro-5-oxa-11-hydroxymethyl-15(R)-19-oxo-PGE₁, a compoundaccording to claim 2.